Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout

NCT04875702 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2021P0005171U01AR080985-01A1
• Study Type: interventional
• Target: 650
• Locations: 1 country
• Sites: 7

Brief Summary

The TRUST study is a randomized, controlled multicenter study to evaluate the management of gout by comparing two commonly used treatment strategies for gout (TTT vs TTASx) to determine the most beneficial for a patient-centered gout outcomes, as well as relevant cardiovascular-metabolic-renal endpoints.

Conditions

Gout

Outcome Measures

Primary Outcomes (1)

• Frequency of gout flare

  number of gout flares occurring during two years of follow-up between the TTT-SU and TTASx groups

  baseline to two years of follow up

Secondary Outcomes (1)

• Quality of life assessment

  baseline to two years of follow up

Study Arms (2)

TTT-SU

ACTIVE COMPARATOR

The participants randomized to the Treat-to-Target-Serum Urate (TTT-SU) group will be counseled about gout, generalized lifestyle and dietary issues and will be provided with a three-month supply of allopurinol as well as a treatment to prophylax against attacks that might occur during the up-titration of urate lowering therapy. Allopurinol dose increases will occur until SU concentrations achieve a target level \< 6.0 mg/dL.

Drug: Allopurinol; Drug: Naproxen 250 MG; Drug: Colchicine 0.6 mg

TTASx

ACTIVE COMPARATOR

Subjects randomized to the treat-to-avoid-symptoms (TTASx) group will receive the same education as the TTT-SU group. In addition, they will receive anti-inflammatory treatments (naproxen, colchicine, and/or prednisone); enough to treat up to six flares over the ensuing three months.

Drug: Allopurinol; Drug: Naproxen 250 MG; Drug: Colchicine 1.2 mg; Drug: Naproxen 500 Mg; Drug: Prednisone 40 mg

Interventions

Allopurinol DRUG

For the TTT-SU group: The dose titration algorithm for allopurinol increases every 4 weeks by 100 mg until the target serum urate of 6 mg/dL is reached or a patient requires 800 mg per day of allopurinol. Subjects will require a blood draw for SU every 4 weeks until reaching the target. For the TTASx group: Subjects randomized to the TTASx group will receive anti-inflammatory treatments (naproxen, colchicine, and/or prednisone) for up to six flares over the ensuing three months. Urate lowering therapy (ULT) will only be offered after the third flare during the trial.

Also known as: Aloprim, Zyloprim

TTASx; TTT-SU

Naproxen 250 MG DRUG

Naproxen 250 mg p.o. twice daily

Also known as: Prophylaxis

TTASx; TTT-SU

Colchicine 0.6 mg DRUG

Colchicine 0.6 mg p.o. once daily

Also known as: Prophylaxis

TTT-SU

Colchicine 1.2 mg DRUG

Dose escalation to 0.6 mg p.o. twice daily for patients experiencing breakthrough flares or a dose decrease (0.6 mg p.o. every other day) for patients experiencing gastrointestinal intolerance.

Also known as: Flare

TTASx

Naproxen 500 Mg DRUG

dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.

Also known as: Flare

TTASx

Prednisone 40 mg DRUG

For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.

Also known as: Flare

TTASx

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Candidates who meet any of the following criteria will be excluded from the study:
• Diagnosis of CKD Stage 3B or worse (eGFR \< 45 mL/min/ 1.73 m2) at screening
• More than one subcutaneous tophus on clinical examination at screening
• Two or more episodes of renal colic in the past 5 years
• Unable to provide informed consent.
• AST/ALT \> 3 × upper limit of normal (ULN) (within 6 months of entry).
• Pregnancy, planning pregnancy, or breastfeeding.
• Patients who have been treated with thiopurines (mercaptopurine (PURINETHOL®), azathioprine (IMURAN®), or thioguanine) in the past 12 months or currently being treated with thiopurines are not eligible for the study. Usage of the thiopurines (azathioprine and mercaptopurine) with allopurinol has been shown to cause a significant drug-drug interaction.
• Unlikely to survive 2 years because of comorbidities.
• Currently taking \> 200 mg of allopurinol per day or any dose of febuxostat. Patients taking 200 mg or less of allopurinol daily may participate, provided they meet the eligibility criteria for flares and current SU, and they have not had a dose escalation in their allopurinol in the previous 6 months.
• Patients with known allergic or hypersensitive reactions to allopurinol and not willing to initiate febuxostat if urate lowering is indicated.
• Subjects that test positive for HLA-B\*5801 allele, a genetic marker for severe cutaneous adverse reactions caused by allopurinol and are unwilling to initiate febuxostat if urate lowering is indicated by the study. Subjects of higher risk, including Black/African American, Asian (except Japanese), native Hawaiian, or Pacific Islander descent will be tested at screening.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (7)

The University of Alabama at Birmingham

South Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

UCLA Health

Santa Monica, California, 90404, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Brigham and Women's Hospital (BWH)

Boston, Massachusetts, 02115, United States

RECRUITING

Boston Medical Center (BMC)

Boston, Massachusetts, 02119, United States

NOT YET RECRUITING

NYU Langone

New York, New York, 10010, United States

RECRUITING

West Virginia University (Including Mobile Clinical Trials Unit)

Morgantown, West Virginia, 26506, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Gout

Interventions

Allopurinol; Naproxen; Colchicine; Solar Activity; Prednisone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Alkaloids; Astronomical Phenomena; Physical Phenomena; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Hyon K Choi, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana D Fernandes, MA

CONTACT

617-643-2140; adfernandes@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 6, 2021
• Study Start: February 22, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)